Singh Jasvinder, Pandit Sreenivas, Bramwell Vincent W, Alpar H Oya
Centre for Drug Delivery Research, University of London School of Pharmacy, London WC1N 1AX, UK.
Methods. 2006 Feb;38(2):96-105. doi: 10.1016/j.ymeth.2005.11.003.
Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.
研究了聚（ε-己内酯）（PCL）、聚（丙交酯-共-乙交酯）（PLGA）-PCL共混物以及包裹白喉类毒素（DT）的共聚物纳米颗粒作为粘膜疫苗递送系统的潜力。采用水包油包水（w/o/w）双乳液溶剂蒸发法制备的纳米颗粒，其释放曲线取决于聚合物的性质。使用Caco-2细胞进行的体外实验表明，与聚合物PLGA、PLGA-PCL共混物和共聚物纳米颗粒相比，PCL纳米颗粒的摄取量显著更高。在鼻腔给药后的体内研究中，使用Caco-2细胞的最疏水纳米颗粒介导的最高摄取量得到了体现。PCL纳米颗粒诱导的DT血清特异性IgG抗体反应显著高于PLGA。肌肉注射后，观察到纳米颗粒的疏水性与免疫反应之间存在显著正相关。在纳米颗粒鼻腔给药后，也观察到纳米颗粒的疏水性与血清DT特异性IgG抗体反应之间的正相关。细胞因子检测表明，根据给药途径的不同，诱导的血清IgG抗体反应也不同，这由IL-6和IFN-γ的不同水平表明。引发最高IgG抗体反应的纳米颗粒不一定引发最高水平的细胞因子IL-6和IFN-γ。
